Reduced immunoregulatory potency of low density lipoproteins with selectively modified arginine and lysine residues of apolipoprotein B.
Human plasma low density lipoproteins (LDL) suppress lymphocyte activation in vitro by inhibiting the early, membrane-associated events such as phytohemagglutinin-enhanced Ca2+ accumulation and phosphatidylinositol turnover. Chemical modification of the arginine residues of the protein constituent of LDL by 1,2-cyclohexanedione/borate or of the lysine residues by reductive methylation substantially decreases the immunosuppressive potency of LDL. The decrease in inhibitory capability of LDL correlates with a reduction in the ability of the derivatized LDL to compete with 125I-labeled LDL for lymphocyte membrane receptors. This correlation indicates that immunoregulation by LDL is the direct result of the binding of LDL to specific receptors at the cell surface. The receptor recognition site of LDL may consist of a high content of basic amino acid residues such that chemical modification of the LDL apolipoprotein reduces the LDL-lymphocyte interaction by specifically altering the change and/or steric properties of the receptor recognition site. Alternatively, chemical modification of arginine or lysine may cause a conformational change of the lipoprotein which is transmitted to the receptor recognition site. Derivatization of lysine or arginine residues does not elicit gross structural alteration of LDL, as evidenced by chemical analysis and by fluorescence quenching analysis. The intrinsic fluorescence intensity of LDL is, however, decreased by chemical modification, indicative of a minor but perhaps biologically significant structural alteration.
D000596:Amino Acids / Q000032:analysis; D001053:Apolipoproteins / Q000276:immunology*; D001055:Apolipoproteins B; D001120:Arginine; D001894:Borohydrides / Q000494:pharmacology; D003512:Cyclohexanones / Q000494:pharmacology; D006801:Humans; D007165:Immunosuppression Therapy; D007454:Iodides / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000276:immunology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D008239:Lysine; D008745:Methylation; D013050:Spectrometry, Fluorescence
D000596:Amino Acids; D001053:Apolipoproteins; D001055:Apolipoproteins B; D001894:Borohydrides; D003512:Cyclohexanones; D007454:Iodides; D008077:Lipoproteins, LDL; C018031:1,2-cyclohexanedione; D001120:Arginine; D008239:Lysine